title: T cell-dependent IgM memory B cells generated during bacterial infection are required for IgG responses to antigen challenge.
abstract: Immunological memory has long considered to be harbored in B cells that express high-affinity class-switched IgG. IgM-positive memory B cells can also be generated following immunization, although their physiological role has been unclear. In this study, we show that bacterial infection elicited a relatively large population of IgM memory B cells that were uniquely identified by their surface expression of CD11c, CD73, and programmed death-ligand 2. The cells lacked expression of cell surface markers typically expressed by germinal center B cells, were CD138 negative, and did not secrete Ab ex vivo. The population was also largely quiescent and accumulated somatic mutations. The IgM memory B cells were located in the region of the splenic marginal zone and were not detected in blood or other secondary lymphoid organs. Generation of the memory cells was CD4 T cell dependent and required IL-21R signaling. In vivo depletion of the IgM memory B cells abrogated the IgG recall responses to specific Ag challenge, demonstrating that the cell population was required for humoral memory, and underwent class-switch recombination following Ag encounter. Our findings demonstrate that T cell-dependent IgM memory B cells can be elicited at high frequency and can play an important role in maintaining long-term immunity during bacterial infection.
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, NY 12201, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Yates
authors.forename: Rachael
authors.initials: R
authors.lastname: Racine
authors.forename: Kevin M
authors.initials: KM
authors.lastname: McBride
authors.forename: Gary M
authors.initials: GM
authors.lastname: Winslow
mesh_terms: D015720:5'-Nucleotidase / Q000378:metabolism; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000008:administration & dosage / Q000276:immunology; D039521:CD11c Antigen / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004536:Ehrlichia / Q000276:immunology; D016873:Ehrlichiosis / Q000276:immunology; D018858:Germinal Center / Q000276:immunology; D007114:Immunization; D017578:Immunoglobulin Class Switching / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology*; D007156:Immunologic Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D061027:Programmed Cell Death 1 Ligand 2 Protein / Q000378:metabolism; D053655:Receptors, Interleukin-21 / Q000378:metabolism; D053668:Syndecan-1 / Q000378:metabolism
chemical_list: D001425:Bacterial Outer Membrane Proteins; D039521:CD11c Antigen; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C556978:Pdcd1lg2 protein, mouse; D061027:Programmed Cell Death 1 Ligand 2 Protein; D053655:Receptors, Interleukin-21; D053668:Syndecan-1; D015720:5'-Nucleotidase